The effect of small, neutral molecules on the binding of sequence specific proteins to DNA is being studied both to understand the energetics underlying this important class of molecular recognition reactions and to develop a method for stabilizing the DNA-protein complexes of activated gene complexes for structural studies using transient electric birefringence and dichroism. The fundamental interaction of sugars with DNA and proteins has been probed through their influence on forces measured by the osmotic stress method coupled with x-ray diffraction. Sugars are preferentially included in the DNA phase. Interaction coefficients scale linearly with sugar molecular weight. These direct force measurements can be connected with experiment. Both the B-Z transition of poly (dG-dC) and the molten globule - random coil transition of myoglobin show osmotic sensitivities that also scale with sugar molecular weight. The osmotic sensitivity of the E. coli galactose operon repressor binding to its operator sequences is being measured. The binding of 2 repressors at sites separated by about 100 bp is necessary for function. The binding of the first is accompanied by the uptake of some 25 extra water molecules; while the binding of the second shows the release of about 200 waters. The binding of the first appears to trigger a protein conformational change exposing extra surface area; while the binding of the second releases this extra bound water through loop formation mediated by protein interactions.